The inheritance of type 2 diabetes and obesity is likely determined by multiple genes. Consequently, the effect of a single susceptibility gene could be small and remain obscured in family-based linkage studies. To complement our genome-wide linkage studies of diabetes and obesity in the Pima Indians, we undertook a genomic association scan by utilizing the AFLP technique for analysis of pooled DNA from subjects that represent the extremes of the studied phenotypes. AFLP is a PCR- based DNA fingerprinting method that allows simultaneous analysis of multiple random polymorphisms. We have performed a dense (1-5cM) AFLP scan comparing DNA pools from subjects with early diabetes (<25y.) vs. non-diabetic controls, and identified 6 markers that differentiate between these groups. A similar, 1cM scan comparing obese vs. lean Pimas yielded 7 differential AFLPs. Studies are in progress to further characterize these markers.We are also exploring AFLP to isolate new markers from the 1q21-q23 genomic region linked with type 2 diabetes in Pimas (see project ZO1-DK69073). This approach is based on capture of AFLPs using large genomic clones (YACs, BACs) spanning 1q21-q23, and analyzing such markers for differences between diabetic and non- diabetic Pimas. This strategy complements project ZO1-DK69073 and will help in identification of candidate genes on 1q21-q23 for further analyses. - Type 2 diabetes mellitus, Pima Indians, Amplified Fragment Length Polymorphism, association - Human Subjects